Primary Hypomagnesemia (Disorder) Clinical Trial
Official title:
Effect of Magnesium Sulfate Infusion Rate on Magnesium Retention in Critically Ill Patients
Hypomagnesemia (low magnesium) is an electrolyte imbalance commonly found in up to 65% of critically ill patients. Possible consequences of hypomagnesemia include neuromuscular and neurologic dysfunction, heart arrhythmias, and alterations in other electrolytes. Data has shown that critically ill patients with hypomagnesemia have a significantly higher mortality rate than patients with a normal magnesium level. The most simple and commonly used test to diagnose hypomagnesemia is a serum magnesium level. Based on the magnesium level and symptoms of hypomagnesemia, patients may be replaced with either oral or intravenous (IV) magnesium. When replacing magnesium via the IV route, approximately half of the dose is retained by the body while the remainder is excreted in the urine. The low retention rate is due to the slow uptake of magnesium by cells and decreased magnesium reabsorption by the kidneys in response to the delivery of a large concentration of magnesium. The purpose of this study is to determine whether an eight hour compared to a four hour infusion of IV magnesium sulfate results in a greater retention of the magnesium dose.
Hypomagnesemia is a common electrolyte disturbance that affects up to 65% of intensive care
unit (ICU) patients with normal renal function. Causes of hypomagnesemia are attributed to
either gastrointestinal (secretory loss, impaired absorption or reabsorption, acute
pancreatitis) or renal losses (alcohol, hypercalcemia, volume expansion, loop or thiazide
diuretics, nephrotoxic medications, renal tubular dysfunction, inborn disorders).
Consequences of magnesium deficiency are not benign and may include neuromuscular and
neurologic dysfunction, cardiac arrhythmias and concomitant electrolyte abnormalities
including hypokalemia and hypocalcemia. Hypomagnesemia has been associated with a
significantly greater mortality rate in critically ill medical patients compared to
normomagnesemic patients. In a study conducted by Rubeiz et al, 46% (17/37) of
hypomagnesemic patients in the medical ICU died compared to 25% (37/147) of normomagnesemic
patients (p < 0.05).
It can be difficult to assess patients for hypomagnesemia because of the unreliable
relationship between serum and tissue magnesium levels. Approximately 1% of total body
magnesium is found in the extracellular fluid while the remaining 99% is distributed among
the bones, muscles, and soft tissues. Approximately 60% of serum magnesium is free ions; 33%
is bound to proteins and 7% is complexed with anions. The most simple and commonly used test
to diagnose hypomagnesemia is the total serum magnesium level which reflects free magnesium
along with complexed and protein bound magnesium. The serum magnesium level, however, is not
always accurate at detecting magnesium deficiency. Patients may appear to be normomagnesemic
based on their serum magnesium level, yet have an underlying magnesium deficiency. Normal
serum magnesium levels vary by laboratory. The normal range of values at Charleston Area
Medical Center (CAMC) is 1.6-2.6 mg/dL.
Magnesium replacement depends on the clinical situation and manifestations. In critical
conditions such as pre-eclampsia, arrhythmias, and tetany, large doses of IV magnesium are
rapidly bolused and often followed by a continuous IV infusion. In asymptomatic patients,
magnesium may be replaced by the oral or IV route depending on the clinical situation. The
dose required to return patients to the normal magnesium range is variable and replacement
may take several doses. Serum magnesium levels are primarily controlled by glomerular
filtration and tubular reabsorption at the sites of the Loop of Henle and distal tubule.
When faced with an increased filtered load of magnesium, the kidney is capable of increasing
its excretion rate. Following intravenous (IV) administration, cellular magnesium uptake is
slow and approximately 50% or more of the infused dose is lost due to increased excretion by
the kidneys and decreased tubular reabsorption.
The investigators current practice in the Medical and Neuroscience ICUs at CAMC General
Hospital is to order 8g of magnesium sulfate for replacement in patients with
hypomagnesemia. When IV magnesium sulfate is ordered the pharmacy automatically sets the
rate to run at 2g per hour unless otherwise specified. Often times the physician will
specify for 8g to be infused over eight hours. The basis of using an extended infusion is
that a slower magnesium infusion rate may increase magnesium retention by allowing a longer
period of time for magnesium uptake by cells and by decreasing the magnesium load delivered
to the kidneys at any given time. As far as the investigators are aware, there have been no
studies completed to date that assess the rate of IV magnesium infusion on the magnesium
retention rate.
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Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment